Pharmaceutical forms for the oral administration of mesna

ABSTRACT

The invention relates to pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, produced by granulation with up to 15% of water, based on the amount of solid employed, and also tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna, produced by direct compression or compaction. without the use of organic solvents.

[0001] Mesna is a known antidote, which is employed for the prophylaxis of the urotoxicity of oxaphosphorines such as ifosphamide and cyclophosphamide. In addition to parenteral formulations, oral formulations are also already known.

[0002] Thus in U.S. Pat. No. 5,503,845, oral formulations in the form of tablets, pellets, capsules having an active compound content of up to >85% of mesna in combination with a preparation process of moist granulation with more than 30% of water, based on the amount of the solids employed, are described. Problems here are the long and uneconomical drying times to be expected as a result of the large amounts of water. Moreover, high amounts of water also lead to active compound instability.

[0003] Effervescent tablets with 10-80% of mesna are further-more disclosed in U.S. Pat. No. 5,358,718. U.S. Pat. No. 5,262,169 describes tablets with 10-80% of mesna. In both abovementioned patent specifications, the claimed composition is coupled with an alcoholic granulation process.

[0004] The use of organic liquids in granulation, however, is to be classified as problematical, since these substances are usually environmentally harmful, and moreover special arrangements are needed for employee protection.

[0005] EP 0468245 describes mesna tablets which contain 10-80% of mesna, in combination with various auxiliaries. Here too, a process for the production of these tablets by means of granulation in the presence of organic solvents is described. The same problems apply as with the abovementioned US patents.

[0006] The object is thus to produce mesna tablets by means of a simple, economical production method and to do this, if possible, without the use of organic solvents. Since mesna is administered in high doses, it is necessary for the oral mesna formulations to have an active compound content of over 80%.

[0007] Surprisingly, it was possible to achieve the object mentioned by producing pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, by granulation with up to 15% of water, based on the amount of solid employed, or pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna by direct compression or compaction. It is to be emphasized that the process for the production of pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules by granulation, direct compression or compaction manages without the use of organic solvents.

[0008] The invention is illustrated in greater detail by means of the following working examples without, however, being restricted thereby.

EXAMPLE 1

[0009] Tablets with 100% of Mesna

[0010] 500 g of mesna are sieved and moistened with 97 g of water (=19.4% based on the solid). The mixture is then granulated, and dried at 40° C. on racks. The granules are compressed to give tablets. Weight: 500 mg Breaking strength: 70-80 N Disintegration: <1.5 min.

EXAMPLE 2

[0011] Tablets with 88% of mesna

[0012] Pure aqueous granulation with 5.6% of water

[0013] 2.7 g of corn starch are dissolved in 3.3 g of water and swollen in 13.7 g of water.

[0014] 300 g of mesna are sieved and kneaded together with swollen corn starch.

[0015] The moist mass is granulated and dried at 40° C. on racks. The dried granules are mixed with 27.0 g of microcrystalline cellulose and 6.0 g of corn starch. 2.7 g of magnesium stearate are then added and mixing is carried out again. Weight: 225.6 mg Breaking strength: 100 N Disintegration: <4 min.

EXAMPLE 3

[0016] Tablets with 81.6% of mesna Compaction.

[0017] 200 g of mesna are sieved together with 30.0 g of lactose and 10.0 g of highly disperse silica and mixed. 5.0 g of magnesium stearate are then added and mixing is carried out again. The mass prepared in this way is compressed to give pressed tablets. The pressed tablets are comminuted and sieved. The material resulting in this way is mixed and processed to give tablets. Weight: 245 mg Breaking strength: 50 N Disintegration: <3 min. 

1. Pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, produced by granulation with up to 15% of water, based on the amount of solid employed.
 2. Pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna, produced by direct compression or compaction.
 3. Process for the production of pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, according to claim 1, by granulation with up to 15% of water, based on the amount of solid employed, without the use of organic solvents.
 4. Process for the production of pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna, according to claim 2, by direct compression or compaction without the use of organic solvents. 